U.S. patent application number 16/459864 was filed with the patent office on 2019-10-24 for application arrangement with a medicinal substance fluid.
The applicant listed for this patent is Fresenius Kabi Austria GmbH. Invention is credited to Roland Gorges, Patricia Grigoleit, Andreas Kerschbaumer, Christian Krenn, Johann Schloegl.
Application Number | 20190321541 16/459864 |
Document ID | / |
Family ID | 47080246 |
Filed Date | 2019-10-24 |
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United States Patent
Application |
20190321541 |
Kind Code |
A1 |
Kerschbaumer; Andreas ; et
al. |
October 24, 2019 |
APPLICATION ARRANGEMENT WITH A MEDICINAL SUBSTANCE FLUID
Abstract
A pharmaceutical product includes a delivery syringe comprising
a plastic receptacle and an oxygen-tight envelope which envelopes
the delivery syringe in an oxygen-tight manner, wherein the plastic
receptacle is filled with an oxygen-sensitive active pharmaceutical
ingredient fluid and an inner surface of the plastic receptacle is
siliconized at least in sections.
Inventors: |
Kerschbaumer; Andreas;
(Worgl, AT) ; Gorges; Roland; (Graz, AT) ;
Grigoleit; Patricia; (Wiesbaden, DE) ; Krenn;
Christian; (Pernegg, AT) ; Schloegl; Johann;
(Wilhering, AT) |
|
Applicant: |
Name |
City |
State |
Country |
Type |
Fresenius Kabi Austria GmbH |
Graz |
|
AT |
|
|
Family ID: |
47080246 |
Appl. No.: |
16/459864 |
Filed: |
July 2, 2019 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
|
|
15377231 |
Dec 13, 2016 |
10350346 |
|
|
16459864 |
|
|
|
|
14433166 |
Apr 2, 2015 |
9522222 |
|
|
PCT/EP2013/070570 |
Oct 2, 2013 |
|
|
|
15377231 |
|
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|
61709657 |
Oct 4, 2012 |
|
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Current U.S.
Class: |
1/1 |
Current CPC
Class: |
B65B 5/045 20130101;
A61M 5/14566 20130101; B65B 7/02 20130101; B65D 81/24 20130101;
A61K 9/107 20130101; B65D 81/266 20130101; A61K 9/0019 20130101;
A61K 31/05 20130101; A61M 5/315 20130101; A61M 5/178 20130101; B65D
81/2069 20130101; B65B 3/003 20130101; A61M 2209/045 20130101; A61M
5/3129 20130101; A61M 5/002 20130101; A61M 5/31511 20130101; A61M
2005/3131 20130101; A61M 2207/00 20130101 |
International
Class: |
A61M 5/00 20060101
A61M005/00; A61M 5/315 20060101 A61M005/315; A61M 5/31 20060101
A61M005/31; B65D 81/24 20060101 B65D081/24; B65D 81/26 20060101
B65D081/26; A61K 9/00 20060101 A61K009/00; A61K 9/107 20060101
A61K009/107; A61K 31/05 20060101 A61K031/05; B65B 7/02 20060101
B65B007/02; B65B 5/04 20060101 B65B005/04; B65B 3/00 20060101
B65B003/00; B65D 81/20 20060101 B65D081/20 |
Foreign Application Data
Date |
Code |
Application Number |
Oct 4, 2012 |
EP |
12187273.3 |
Claims
1. A pharmaceutical product comprising: a delivery syringe
comprising a transparent plastic receptacle, wherein the plastic
receptacle is filled with an oxygen-sensitive active pharmaceutical
ingredient fluid; and an oxygen-tight envelope which envelopes the
delivery syringe in an oxygen-tight manner,wherein the oxygen-tight
envelope has an oxygen transmission rate of less than or equal to
10 cm3/m2 d bar and a water vapor transmission rate of less than or
equal to 10 g/m2 d.
2. The pharmaceutical product of claim 1, wherein the
oxygen-sensitive active pharmaceutical ingredient fluid is an
active pharmaceutical ingredient emulsion.
3. The pharmaceutical product of claim 1, wherein the active
pharmaceutical ingredient fluid comprises an active pharmaceutical
ingredient having a water solubility in which at least 30 ml of
water are required to dissolve 1 g of active pharmaceutical
ingredient.
4. The pharmaceutical product of claim 1, wherein the active
pharmaceutical ingredient fluid comprises propofol.
5. The pharmaceutical product of claim 1, wherein the plastic
receptacle is formed from plastic comprising cyclic olefin
copolymer, cyclic olefin polymer, Crystal Clear Polymer, or a
combination thereof.
6. The pharmaceutical product of claim 1, wherein the delivery
syringe comprises a plastic plunger rod storable in a shiftable
manner in the plastic receptacle.
7. The pharmaceutical product of claim 6, wherein the plastic
plunger rod is formed from plastic comprising cyclic olefin
copolymer, cyclic olefin polymer, Crystal Clear Polymer,
polypropylene, or a combination thereof.
8. The pharmaceutical product of claim 1, wherein the plastic
receptacle and/or the plastic plunger rod is/are stored in an at
least axially shiftable manner in the oxygen-tight envelope.
9. The pharmaceutical product of claim 1, wherein the plastic
receptacle and/or the plastic plunger rod are stored at least
separately by means of at least one flexible spacer.
10. The pharmaceutical product of claim 1, wherein the oxygen-tight
envelope comprises an ethylene-vinyl alcohol copolymer barrier.
11. The pharmaceutical product of claim 1, wherein the oxygen-tight
envelope comprises a shell which is thermoformed from
thermoplastic, and wherein the shell forms a molding for the
formfitting accommodation of the delivery syringe.
12. The pharmaceutical product of claim 11, wherein the
thermoplastic comprises an amorphous polyethylene terephthalate
film comprising an ethylene-vinyl alcohol copolymer barrier or
biaxially oriented polyester comprising an ethylene-vinyl alcohol
copolymer barrier.
13. The pharmaceutical product of claim 11, wherein the shell is
sealed in an oxygen-tight manner with a peelable polyethylene film
or a polyethylene film comprising an ethylene-vinyl alcohol
copolymer barrier.
14. The pharmaceutical product of claim 1, wherein the plastic
receptacle is sealed in a fluid-tight manner at the distal and
proximal ends by a detachable closure.
15. The pharmaceutical product of claim 1, comprising an oxygen
absorber.
16. A pharmaceutical product comprising: a delivery syringe
comprising a plastic receptacle, wherein the plastic receptacle is
transparent and filled with an oxygen-sensitive active
pharmaceutical ingredient fluid; and an oxygen-tight envelope which
envelopes the delivery syringe in an oxygen-tight manner, wherein
the oxygen-tight envelope has an oxygen transmission rate of less
than or equal to 10 cm.sup.3/m.sup.2 d bar and a water vapor
transmission rate of less than or equal to 10 g/m.sup.2 d, wherein
the oxygen-sensitive active pharmaceutical ingredient fluid is an
active pharmaceutical ingredient emulsion and comprises propofol
and wherein the plastic receptacle is formed from plastic
comprising cyclic olefin copolymer, cyclic olefin polymer, Crystal
Clear Polymer, or a combination thereof; and wherein an inner
surface of the plastic receptacle is siliconized at least in
sections.
17. A method for producing the pharmaceutical product of claim 1,
comprising: providing a delivery syringe comprising a transparent
plastic receptacle; filling the plastic receptacle with an
oxygen-sensitive active pharmaceutical ingredient fluid;
oxygen-tight enveloping of the delivery syringe comprising the
filled plastic receptacle by means of an oxygen-tight envelope
wherein the oxygen-tight envelope has an oxygen transmission rate
of less than or equal to 10 cm.sup.3/m.sup.2 d bar and a water
vapor transmission rate of less than or equal to 10 g/m.sup.2 d;
and, optionally, placing an oxygen absorber in the oxygen-tight
envelope and/or filling the oxygen-tight envelope with a fluid
which is low in oxygen or binds oxygen.
18. The pharmaceutical product of claim 1, comprising a fluid which
is low in oxygen or binds oxygen.
19. The pharmaceutical product of claim 1, wherein the oxygen-tight
envelope is transparent.
Description
[0001] This application is a continuation of U.S. patent
application Ser. No. 15/377,231, filed Dec. 13, 2016, which is a
continuation of Ser. No. 14/433,166, filed Apr. 2, 2015, which is
the U.S. National Phase of International Application No.
PCT/EP2013/070570, filed Oct. 2, 2013, which claims priority to
U.S. Provisional Patent Application 61/709,657, filed Oct. 4, 2012,
and European Patent Application No. 12187273.3, filed Oct. 4, 2012,
the contents of which are incorporated herein.
[0002] The present invention relates to the field of administering
active pharmaceutical ingredients.
[0003] The administration of active pharmaceutical ingredients
typically involves using delivery syringes operable either by hand
or by using a pump system. Conventional delivery syringes comprise
a receptacle fillable with an active pharmaceutical ingredient, and
also a plunger stored in a shiftable manner in the receptacle for
the administration of the active pharmaceutical ingredient.
[0004] Active pharmaceutical ingredients administrable using a
delivery syringe can be in the form of an active pharmaceutical
ingredient emulsion fillable into a receptacle of a delivery
syringe. In the case of oxygen-sensitive active pharmaceutical
ingredients such as propofol, said active pharmaceutical ingredient
emulsions are therefore typically stored in glass containers, such
as glass bottles or vials for example. Thus, the active
pharmaceutical ingredient can be stored in an oxygen-tight manner
just before use and, when needed, transferred to a delivery syringe
comprising a receptacle and then administered. However, such
storage of active pharmaceutical ingredients is elaborate and
therefore expensive. Also, the separate transfer of liquid can lead
to contamination of the active pharmaceutical ingredient.
[0005] In the publication WO 94/25089, it was therefore proposed
that delivery syringes comprising glass receptacles be used for
directly storing therein the propofol sensitive to oxygen. However,
delivery syringes comprising glass receptacles are not resistant to
breakage. As a result, the clamping of such glass receptacles in
pump syringe systems is problematic.
[0006] It is therefore an object of the present invention to
provide an efficient concept for the storage of oxygen-sensitive
active pharmaceutical ingredients in receptacles of delivery
syringes.
[0007] This object is achieved by the features of the independent
claims. Advantageous developments are subject matter of the
dependent claims, the description and the drawings.
[0008] The present invention is based on the insight that the above
object can be achieved by using a delivery syringe plastic
receptacle which is prefilled with oxygen-sensitive active
pharmaceutical ingredient and which is enveloped in an oxygen-tight
manner by means of an oxygen-tight envelope. This makes it possible
to store oxygen-sensitive active pharmaceutical ingredients in
prefilled and oxygen-penetratable plastic receptacles of delivery
syringes even over a relatively long period.
[0009] The oxygen-tight envelope can, for example in the form of
outer packaging or a blister, accommodate the delivery syringe
comprising the prefilled plastic receptacle and protect it against
the intrusion of oxygen.
[0010] According to one aspect, the invention provides a delivery
arrangement comprising a delivery syringe comprising a plastic
receptacle, wherein the plastic receptacle is filled with an
oxygen-sensitive active pharmaceutical ingredient fluid, and an
oxygen-tight envelope which envelopes the delivery syringe in an
oxygen-tight manner, preferably wherein an inner surface of the
plastic receptacle is siliconized at least in sections. This
siliconization can in particular increase the sliding capacity of a
plunger in the plastic receptacle and additionally protect the
active pharmaceutical ingredient fluid.
[0011] According to a further aspect, the invention provides a
delivery arrangement comprising a delivery syringe comprising a
plastic receptacle, wherein the plastic receptacle is filled with
an oxygen-sensitive active pharmaceutical ingredient fluid; and an
oxygen-tight envelope which envelopes the delivery syringe in an
oxygen-tight manner, wherein the oxygen-sensitive active
pharmaceutical ingredient fluid is an active pharmaceutical
ingredient emulsion and comprises propofol and wherein the plastic
receptacle is formed from plastic comprising at least one cyclic
olefin copolymer and wherein an inner surface of the plastic
receptacle is siliconized at least in sections. Such a plastic
receptacle is in particular resistant to propofol acting as
solvent. At the same time, the propofol is in particular
effectively protected from the oxygen present in the
environment.
[0012] The oxygen-tight envelope preferably encloses the delivery
syringe comprising the filled plastic receptacle, making it
possible, even in the case of oxygen-penetratable plastics, to
protect the active pharmaceutical ingredient stored in the plastic
receptacle against oxygen. The internal space which is enclosed by
the envelope and in which the delivery syringe is arranged can be
additionally evacuated in order to reduce the oxygen density.
However, the internal space enclosed by the envelope can also be
filled with a fluid, such as gas or liquid, which is low in oxygen
or binds oxygen.
[0013] The oxygen-tight envelope has an oxygen transmission rate of
less than or equal to 10 cm.sup.3/m.sup.2 d bar, preferably of less
than or equal to 5 cm.sup.3/m.sup.2 d bar, particularly preferably
less than or equal to 2 cm.sup.3/m.sup.2 d bar. Oxygen transmission
rate or oxygen-tightness is determined by the information in the
standard DIN 53380.
[0014] Moreover, the oxygen-tight envelope also provides a barrier
against water vapor. The oxygen-tight envelope has a water vapor
transmission rate of less than or equal to 10 g/m.sup.2 d,
preferably of less than or equal to 5 g/m.sup.2 d, particularly
preferably less than or equal to 3 g/m.sup.2 d. Water vapor
transmission rate is determined by the information in the standard
DIN 53122.
[0015] The plastic receptacle can be completely filled or only
partially filled with the active pharmaceutical ingredient
fluid.
[0016] The delivery syringe can be formed solely by the filled
plastic receptacle. In one embodiment, the delivery syringe can
comprise a plastic plunger rod. The plastic plunger rod can be a
component of the delivery arrangement. However, in one embodiment,
the plastic plunger rod is not a component of the delivery
arrangement.
[0017] In one embodiment, the oxygen-sensitive active
pharmaceutical ingredient fluid is an active pharmaceutical
ingredient emulsion.
[0018] In one embodiment, the active pharmaceutical ingredient
fluid comprises an active pharmaceutical ingredient having poor
water solubility, with at least 30 ml of water being required to
dissolve 1 g of active pharmaceutical ingredient. Therefore, by
using the oxygen-tight envelope, it is possible for an entire group
of oxygen-sensitive active pharmaceutical ingredients to be stored
long-term.
[0019] In one embodiment, the active pharmaceutical ingredient
fluid is or comprises propofol, more particularly a propofol
emulsion. Propofol is described by the chemical name
2,6-diisopropylphenol (IUAPC).
[0020] In one embodiment, the plastic receptacle is formed from a
cyclic polymer, preferably from a cyclic polyolefin. The plastic
receptacle can be formed from plastic comprising one of the
following polymers: cyclic olefin copolymer, cyclic olefin polymer
or Crystal Clear Polymer. Such a plastic receptacle is resistant to
solvents. More particularly, such a plastic receptacle can be used
for storing propofol acting as solvent.
[0021] In one embodiment, the delivery arrangement or delivery
syringe further comprises a plastic plunger rod storable in a
shiftable manner in the plastic receptacle, and the plastic plunger
rod is in particular arranged beside the plastic receptacle and
enveloped in an oxygen-tight manner by means of the oxygen-tight
envelope.
[0022] In one embodiment, the delivery syringe can basically
comprise only the filled plastic receptacle, which is enveloped in
an oxygen-tight manner. The plastic plunger rod can then be
provided separately. In said embodiment, an oxygen-tight envelope
is not required for packaging the plastic plunger rod.
[0023] In one embodiment, the plastic plunger rod is formed from
plastic comprising one of the following polymers: cyclic olefin
copolymer, cyclic olefin polymer or Crystal Clear Polymer, or it is
formed from polypropylene.
[0024] In a further embodiment of the invention, the plastic
receptacle and/or the plastic plunger rod is/are stored in an at
least axially shiftable manner in the oxygen-tight envelope. As a
result, in the event of a lateral impact, for example axial impact,
it is possible for the plastic receptacle and/or the plastic
plunger rod to carry out a compensatory movement, for example in
the direction of the opposite side, more particularly without
themselves being damaged and/or without the shell being damaged. In
one embodiment of the invention, the plastic receptacle and/or the
plastic plunger rod and the envelope is/are configured such that
the two end sides of the plastic receptacle and/or the two end
sides of the plastic plunger rod are in each case positionable at a
distance from about 0.5 cm to about 2 cm from the inner surface of
the envelope. This provides sufficient space to allow an axial
compensatory movement.
[0025] In a further embodiment of the invention, the plastic
receptacle and the plastic plunger rod are stored at least
separately by means of at least one flexible spacer, preferably
elastic spacer. As a result, impacts in a direction transverse to
the longitudinal axis of the plastic receptacle and/or the plastic
plunger rod can be absorbed. In one embodiment, the at least one
spacer has a width from about 0.3 cm to about 1.5 cm.
[0026] In one embodiment, the oxygen-tight envelope comprises an
ethylene-vinyl alcohol copolymer barrier, more particularly an
ethylene-vinyl alcohol copolymer layer. The presence of the
ethylene-vinyl alcohol copolymer barrier makes the envelope
oxygen-tight. The ethylene-vinyl alcohol copolymer barrier can, for
example, be designed in the form of an ethylene-vinyl alcohol
copolymer layer with which the envelope is sealed. However, the
ethylene-vinyl alcohol copolymer barrier can be directly provided
in plastic from which the oxygen-tight envelope can be
produced.
[0027] In one embodiment, the oxygen-tight envelope can be
constructed from multilayer plastic. The plastic layers can, for
example, comprise a polyethylene terephthalate film comprising an
ethylene-vinyl alcohol copolymer barrier or polyester comprising an
ethylene-vinyl alcohol copolymer barrier. The multilayer plastic
can further comprise a peelable polyethylene film, more
particularly sealed in an oxygen-tight manner with an
ethylene-vinyl alcohol copolymer barrier.
[0028] In one embodiment, the oxygen-tight envelope comprises a
shell which is formed from thermoplastic, and is more particularly
thermoformed. The shell can, for example, be thermoformed in order
to accommodate the delivery syringe.
[0029] In one embodiment, the shell forms a molding for the
formfitting accommodation of the delivery syringe. In this way, the
delivery syringe is held in the shell in a formfitting manner. The
molding forming the shell can further comprise formfitting
accommodation for the plunger rod. The formfitting accommodation in
each case can be realized each time by a depression in a shell
base. The shell can further be formed such that it is possible to
lock the delivery syringe in place therein. For instance, the shell
formed as a molding can, for example, laterally comprise latching
projections which are elastic and, upon insertion of the plastic
receptacle and/or the plastic plunger rod, are initially displaced
and then return to their original position, making it possible to
fix the delivery syringe. In one embodiment, the shell has a wall
thickness within a range from 50 .mu.m to 5000 .mu.m, preferably
from 10 .mu.m to 1000 .mu.m. Measurement is carried out in
accordance with DIN 53370.
[0030] In one embodiment, the thermoplastic comprises an amorphous
polyethylene terephthalate film comprising an ethylene-vinyl
alcohol copolymer barrier or biaxially oriented polyester
comprising an ethylene-vinyl alcohol copolymer barrier. In one
embodiment, the thermoplastic forming the shell has a basis weight
within a range from 50 g/m.sup.2 to 5000 g/m.sup.2, preferably from
300 g/m.sup.2 to 1000 g/m.sup.2. Measurement is carried out in
accordance with ISO 2286-2.
[0031] In one embodiment, the shell is sealed in an oxygen-tight
manner with a peelable film or polyethylene film or a polyethylene
film comprising an ethylene-vinyl alcohol copolymer barrier. In one
embodiment, the peelable film has a thickness within a range from
10 .mu.m to 2000 .mu.m, preferably from 50 .mu.m to 300 .mu.m.
Measurement is carried out in accordance with DIN 53370. In one
embodiment, the peelable film has a basis weight within a range
from 10 g/m.sup.2 to 1000 g/m.sup.2, preferably from 50 g/m.sup.2
to 200 g/m.sup.2. Measurement is carried out in accordance with ISO
2286-2.
[0032] In one embodiment, the oxygen-tight envelope comprises a
further shell formed from thermoplastic, more particularly a shell
formed from thermoplastic, wherein the further shell comprises an
ethylene-vinyl alcohol copolymer barrier, and wherein the further
shell is joined, more particularly welded or adhesively bonded, to
the shell in an oxygen-tight manner. The further shell can, for
example, likewise form a molding for the formfitting accommodation
of the delivery syringe. The delivery syringe is therefore held,
firstly, by a shell forming a lower part and, secondly, by a lid or
by an upper part formed by the further shell. The shell and the
further shell are, for example, joined in an oxygen-tight manner
along a connecting joint, and this can be realized by welding or
adhesive bonding. The shells joined to one another therefore form a
stable envelope which can safely accommodate the prefilled plastic
receptacle. The further shell can likewise be constructed from
plastic and have the same material composition as the shell.
[0033] In one embodiment, the plastic receptacle is sealed in a
fluid-tight manner at the distal and proximal ends by a detachable
closure in each case. The detachable closures can, for example, be
designed as plugs or stoppers or plungers or as screw caps. This
prevents the active pharmaceutical ingredient fluid from leaking
out. The distal-side closure of the plastic receptacle can be
formed by a plunger into which it is possible to insert or screw in
a plastic plunger rod.
[0034] In one embodiment, the delivery arrangement can comprise an
oxygen absorber which can, for example, comprise iron powder. The
oxygen absorber can be introducible into the shell of the envelope
or be joined to the shell.
[0035] In one embodiment, the inner surface of the plastic
receptacle and/or the outer surface of the plunger and/or the outer
surface of the closure is siliconized, more particularly coated
with silicone, at least in sections, preferably completely. This
increases the sliding capacity thereof. Furthermore, this
additionally protects the active pharmaceutical ingredient.
[0036] According to a further aspect, the invention provides a
method for producing the delivery arrangement according to the
invention. The method comprises the steps of providing a delivery
syringe comprising a plastic receptacle, of filling the plastic
receptacle with an oxygen-sensitive active pharmaceutical
ingredient fluid, more particularly with propofol, and of
enveloping the delivery syringe comprising the filled plastic
receptacle in an oxygen-tight manner by means of an oxygen-tight
envelope.
[0037] Further features of the production method are directly
revealed by the structure of the delivery arrangement according to
the invention and by the production steps required in particular
for producing the aforementioned plastics.
[0038] Further embodiments are more particularly elucidated with
reference to the attached drawings. What are shown are:
[0039] FIG. 1 a diagrammatic view of a delivery arrangement;
[0040] FIGS. 2a, b diagrammatic side views of a delivery
arrangement; and
[0041] FIG. 3 a flowchart of a production method for producing a
delivery arrangement.
[0042] FIG. 1 shows diagrammatically a delivery arrangement
according to one embodiment. The delivery arrangement comprises a
delivery syringe 100 comprising a plastic receptacle 101 and a
plastic plunger rod 103. The plunger rod 103 comprises, at the
distal end thereof, an insert 105 which is introducible into a
plunger 113. Here, for example, the plastic plunger rod 103 is
stored outside the plastic receptacle 101.
[0043] The plastic receptacle 101 is, as indicated in FIG. 1,
filled with an active pharmaceutical ingredient fluid 107,
preferably with propofol. The plastic receptacle 101 comprises, at
the proximal side, a nozzle 109 which is sealed with a closure 111,
for example with a plastic cap. The nozzle 109 has a, preferably
male, Luer connector or Luer-Lock connector.
[0044] The plastic receptacle 101 is, at the distal side, closed
off with a plunger 113 into which it is possible to introduce, for
example screw in, the insert 105. In this way, the plastic plunger
rod 103 can be completed by the plunger 113. The plunger 113
therefore also simultaneously serves as a distal closure of the
plastic receptacle 101. In one embodiment, the plastic plunger rod
103 can already have a plunger instead of the insert 105. In this
case, the plunger receptacle 101 is provided at the distal side
with a further closure.
[0045] Also at the distal side, the plastic receptacle 101
comprises side wings 115, 117 which allow not only manual
administration but also use of the delivery syringe in a pump
system.
[0046] The delivery arrangement further comprises an oxygen-tight
envelope 119 which can, for example, be formed as a blister or as
packaging and envelopes the delivery syringe 100 completely and in
an oxygen-tight manner.
[0047] In one embodiment, the oxygen-tight envelope 119 can
comprise an oxygen-tight shell 121 and also an oxygen-tight film
123 which seals the shell 121 in an oxygen-tight manner along an
edge 125 of the shell 121.
[0048] To this end, the shell 121 can be formed from a transparent
thermoforming film based on an APET film comprising an EVOH barrier
(EVOH: ethylene vinyl alcohol) and a peelable sealing layer
composed of polyethylene. The shell 121 is therefore a good oxygen
barrier and has high rigidity and also good thermoforming behavior,
allowing the shell 121 to be designed as a molding. The shell 121
can have at least one of the following technical properties:
[0049] Total thickness: 500 .mu.m, DIN 53370; basis weight: 646
g/m.sup.2, ISO 2286-2; oxygen transmission rate: <1
cm.sup.3/m.sup.2 d bar, 23.degree. C./35% r.h., DIN 53380; water
vapor transmission rate: <1 g/m.sup.2 d, 23.degree. C./85% r.h.,
DIN 53122.
[0050] The film 123 can, for example, be a polyethylene film
comprising an EVOH barrier and, as result, likewise be
oxygen-tight. The film 123 can further likewise be produced on the
basis of an APET film (APET: amorphous polyethylene terephthalate),
making it possible to realize an elevated rigidity. The film 123
is, for example, joined along the edge 125 to the shell 121 in an
oxygen-tight manner, for example by welding or adhesive
bonding.
[0051] The shell 121 can be provided as a molding for the
formfitting accommodation of the plastic receptacle 101 and the
plunger 113. To this end, the shell 121 can comprise an
accommodating recess 127 for the accommodation of the plastic
receptacle 101 and an accommodating recess 129 for the
accommodation of the plastic plunger rod 103.
[0052] To hold the plastic receptacle 101, the accommodating recess
127 can comprise clamping projections 131. The accommodating recess
129 can comprise clamping projections 133 to hold the plastic
plunger rod 103. The clamping projections 131, 133 are elastic and
therefore able to be pushed in upon application of the plastic
receptacle 101 and the plastic plunger rod 103, respectively. Owing
to the elasticity of the clamping projections 131, 133, they exert
a force, for example in a radial direction, on the plastic
receptacle 101 and on the plastic plunger rod 103, respectively,
making it possible to fix these elements. In one embodiment, the
elements 101 and/or 103 can be fixed such that they cannot fall out
of the holder, but are at the same time still shiftable in an axial
direction. As a result, in the event of an axial impact for
example, it is possible for the plastic receptacle 101 and/or the
plastic plunger rod 103 to carry out an axial compensatory
movement, more particularly without themselves being damaged and/or
without the shell 121 being damaged.
[0053] The accommodating recess 127 for the accommodation of the
plastic receptacle 101 and the accommodating recess 129 for the
accommodation of the plastic plunger rod 103 are arranged
separately by means of at least one spacer 130. In the embodiment
shown, they are arranged separately by means of two spacers 130.
Arranged on the spacers 130 are the aforementioned clamping
projections 131, 133. The spacers 130 are flexible, preferably
elastic. As a result, impacts in a direction transverse to the
longitudinal axis of the plastic receptacle 101 and/or the plastic
plunger rod 103 can be cushioned. The two spacers 130 are each
provided by a type of wall section.
[0054] In one embodiment, the shell 121 and/or the film 123 can be
formed from a plastic composite composed of biaxially oriented
polyester comprising a coextruded sealing barrier layer composed of
polyethylene, EVOH, polyethylene. Such a plastic composite is
notable for good transparency. Furthermore, it is possible to
realize a broad sealing area and a good oxygen barrier. A film 123
formed in this manner can be used in particular as a lid film for
sealing thermoformed shells, for example the shell 121. The film
123 can have at least one of the following technical
properties:
[0055] total thickness: 100 .mu.m, DIN 53370; basis weight: 107.5
g/m.sup.2, ISO 2286-2; longitudinal tensile strength: 40-60
N/mm.sup.2, ISO 527-3; transverse tensile strength: 35-55
N/mm.sup.2, ISO 527-3; longitudinal elongation at break: 40-120%,
ISO 527-3; transverse elongation at break: 40-120%, ISO 527-3;
oxygen transmission rate: 1 cm.sup.3/m.sup.2 d bar, 23.degree.
C./35% r.h., DIN 53380; CO.sub.2 transmission rate: <4
cm.sup.3/m.sup.2 d bar, 23.degree. C./35% r.h., DIN 53380; N.sub.2
transmission rate: <1 cm.sup.3/m.sup.2 d bar, 23.degree. C./35%
r.h., DIN 53380.
[0056] In one embodiment, the plastic receptacle 101 is formed from
a cyclic polymer. Cyclic polymers have a high purity and also a
resistance, ensuring a relatively long storage of active
pharmaceutical ingredients. However, cyclic polymers are
oxygen-penetrable or oxygen-permeable. This oxygen permeability is
disadvantageous not only for oxygen-sensitive products, such as
oil-in-water emulsions, but also for oxygen-sensitive active
pharmaceutical ingredients, such as propofol.
[0057] In one embodiment, this oxygen permeability of the plastic
receptacle 101 is compensated for by providing the envelope 119,
which can be constructed from a plastic blister and can have a
barrier layer with respect to oxygen.
[0058] In one embodiment, the plastic receptacle 101 is formed from
COC (cyclic olefin copolymer), COP (cyclic olefin polymer) or CCP
(Crystal Clear Polymer). These have been found to be resistant to
propofol acting as solvent. The plunger 113 and/or the closure 111
is, for example, formed from rubber, more particularly from
bromobutyl. The plastic plunger rod 103 can, for example, be formed
from polypropylene.
[0059] In one embodiment, the plastic receptacle 101 can be a
transparent plastic selected from the group of cyclic olefin
copolymers or cyclic olefin polymers. The envelope 119 forms an
oxygen-impenetrable packaging which encloses the plastic receptacle
101 filled with the active pharmaceutical ingredient fluid 107.
[0060] In one embodiment, the inner surface of the plastic
receptacle 101 is siliconized or coated with silicone. This
increases the sliding capacity thereof. Furthermore, this
additionally protects the active pharmaceutical ingredient.
[0061] In a further embodiment, plunger 113 is siliconized at least
in sections. In one embodiment, the closure 11 is also siliconized
at least in sections.
[0062] FIGS. 2a and 2b show different side views of the delivery
arrangement shown in FIG. 1. In one embodiment, the delivery
arrangement can comprise a nonfluidic oxygen absorber 135, which
can, for example, comprise iron dust. The oxygen absorber 135 is,
for example, arranged at the base of the shell 121.
[0063] FIG. 3 shows a chart of a method for producing a delivery
arrangement. The method 300 comprises step 301 of providing a
delivery syringe comprising a plastic receptacle, step 303 of
filling the plastic receptacle with an oxygen-sensitive active
pharmaceutical ingredient fluid, for example with propofol or with
a propofol fluid, more particularly a propofol emulsion, and
oxygen-tight enveloping 305 of the delivery syringe comprising the
filled plastic receptacle by means of an oxygen-tight envelope. The
method further comprises the step of arranging the prefilled
plastic receptacle 101 and the plastic plunger rod 103 in the
thermoformed shell 121 and also the oxygen-tight sealing of the
shell 121 with the lid film 123 by means of, for example, welding
or adhesive bonding.
[0064] In one embodiment, an advantage of the delivery arrangement
is the ease of use thereof without the need to transfer an active
pharmaceutical ingredient to further containers. Furthermore, the
delivery syringe can be directly removed and used without the need
for further assembly steps. The plastic receptacle 101 has, for
example, a capacity of 50 ml, making it possible for the plastic
receptacle to be automatically recognized by conventional pump
systems. The use of the plastic receptacle achieves a resistance to
breakage that is increased with respect to glass. Furthermore,
waste quantity can be reduced coupled with simultaneous time
savings as a result of elimination of administration preparation
steps, which are, for example, caused by transfer of the active
pharmaceutical ingredient.
LIST OF REFERENCE SIGNS
[0065] 100 Delivery syringe [0066] 101 Plastic receptacle [0067]
103 Plastic plunger rod [0068] 105 Insert [0069] 107 Active
pharmaceutical ingredient fluid [0070] 109 Nozzle [0071] 111
Closure [0072] 113 Plastic plunger [0073] 115 Side wing [0074] 117
Side wing [0075] 119 Oxygen-tight envelope [0076] 121 Shell [0077]
123 Film [0078] 125 Edge [0079] 127 Accommodating recess for the
delivery syringe [0080] 129 Accommodating recess for the plunger
rod [0081] 130 Spacer or wall section between the accommodating
recess for the delivery syringe and the accommodating recess for
the plunger rod [0082] 131 Clamping projection [0083] 133 Clamping
projection [0084] 135 Oxygen absorber [0085] 300 Method [0086] 301
Providing step [0087] 303 Filling step [0088] 305 Oxygen-tight
enveloping
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